Old Yellow Enzyme-mediated reduction of β-cyano-α,β-unsaturated esters for the synthesis of chiral building blocks: stereochemical analysis of the reaction

Brenna, Elisabetta; Gatti, Francesco G.; Manfredi, Alessia; Monti, Daniela; Parmeggiani, Fabio

doi:10.1039/c3cy20804d

Cited by 38 publications

(25 citation statements)

References 61 publications

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“…In particular, α,β-unsaturated carbonylic compounds (e.g. [26][27][28][29][30] More recently, it has been shown that an electron-withdrawing halogen group in the α-position can significantly increase the reactivity of α,β-unsaturated esters towards bio-reduction. 17,18,[19][20][21][22] In contrast, alkenes bearing a single conjugated ester moiety or a free carboxylic group are poorly reduced or not converted at all.…”

Section: Introductionmentioning

confidence: 99%

Systematic methodology for the development of biocatalytic hydrogen-borrowing cascades: application to the synthesis of chiral α-substituted carboxylic acids from α-substituted α,β-unsaturated aldehydes

et al. 2015

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Ene-reductases (ERs) are flavin dependent enzymes that catalyze the asymmetric reduction of activated carbon-carbon double bonds. In particular, α,β-unsaturated carbonyl compounds (e.g. enals and enones) as well as nitroalkenes are rapidly reduced. Conversely, α,β-unsaturated esters are poorly accepted substrates whereas free carboxylic acids are not converted at all. The only exceptions are α,β-unsaturated diacids, diesters as well as esters bearing an electron-withdrawing group in α- or β-position. Here, we present an alternative approach that has a general applicability for directly obtaining diverse chiral α-substituted carboxylic acids. This approach combines two enzyme classes, namely ERs and aldehyde dehydrogenases (Ald-DHs), in a concurrent reductive-oxidative biocatalytic cascade. This strategy has several advantages as the starting material is an α-substituted α,β-unsaturated aldehyde, a class of compounds extremely reactive for the reduction of the alkene moiety. Furthermore no external hydride source from a sacrificial substrate (e.g. glucose, formate) is required since the hydride for the first reductive step is liberated in the second oxidative step. Such a process is defined as a hydrogen-borrowing cascade. This methodology has wide applicability as it was successfully applied to the synthesis of chiral substituted hydrocinnamic acids, aliphatic acids, heterocycles and even acetylated amino acids with elevated yield, chemo- and stereo-selectivity. A systematic methodology for optimizing the hydrogen-borrowing two-enzyme synthesis of α-chiral substituted carboxylic acids was developed. This systematic methodology has general applicability for the development of diverse hydrogen-borrowing processes that possess the highest atom efficiency and the lowest environmental impact.

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Section: Introductionmentioning

confidence: 99%

Systematic methodology for the development of biocatalytic hydrogen-borrowing cascades: application to the synthesis of chiral α-substituted carboxylic acids from α-substituted α,β-unsaturated aldehydes

et al. 2015

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“…All enzymes tested showed (R)-selectivity and up to 99% enantioselectivity (the absolute configuration of the pharmaceutical building block, compound 18b, was not specified) [47]. Recently published studies describe the hydrogenation of a library of β-cyano-α,β-unsaturated acids and esters using ERs from the OYE family [48,49]. For example, a biocatalytic route for GABA analogues, such as pregabalin could be provided ( Figure 18.4c).…”

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confidence: 99%

Ene‐reductases and their Applications

2016

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“…[1][2][3] At the same time, the substances containing β-cyano-α,β-unsaturated ketone moieties also have great potential application value. [1][2][3] At the same time, the substances containing β-cyano-α,β-unsaturated ketone moieties also have great potential application value.…”

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confidence: 99%

“…β-Cyano-α,β-unsaturated ketones contain important functional groups, such as cyano, carbonyl and alkenyl, which are significant intermediates for the synthesis of fine chemicals, such as pharmaceuticals, pesticides and perfumes. [1][2][3] At the same time, the substances containing β-cyano-α,β-unsaturated ketone moieties also have great potential application value. [4] Figure 1 shows two structures which can separately be used as a calciumchannel blocker (treating hypertension, cerebral artery occlusion [5] and Alzheimer's disease [6] ) and a new type of near-infrared dye.…”

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confidence: 99%

Palladium‐Catalyzed One‐Pot Four‐Component Synthesis of β‐Cyano‐α,β‐unsaturated Ketones Using Calcium Carbide as an Acetylene Source and Potassium Hexacyanoferrate(II) as an Eco‐Friendly Cyanide Source

Hao

2019

Adv Synth Catal

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Palladium-catalyzed one-pot four-component synthesis of β-cyano-α,β-unsaturated ketones by the reactions of aryl halides, calcium carbide, potassium hexacyanoferrate(II) and aroyl chlorides is described. The salient features of this protocol are the direct use of easy-to-handle acetylene source and eco-friendly cyanide source, wide scope of substrates with good functional group tolerance, and simple work-up procedure.

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Old Yellow Enzyme-mediated reduction of β-cyano-α,β-unsaturated esters for the synthesis of chiral building blocks: stereochemical analysis of the reaction

Cited by 38 publications

References 61 publications

Systematic methodology for the development of biocatalytic hydrogen-borrowing cascades: application to the synthesis of chiral α-substituted carboxylic acids from α-substituted α,β-unsaturated aldehydes

Systematic methodology for the development of biocatalytic hydrogen-borrowing cascades: application to the synthesis of chiral α-substituted carboxylic acids from α-substituted α,β-unsaturated aldehydes

Ene‐reductases and their Applications

Palladium‐Catalyzed One‐Pot Four‐Component Synthesis of β‐Cyano‐α,β‐unsaturated Ketones Using Calcium Carbide as an Acetylene Source and Potassium Hexacyanoferrate(II) as an Eco‐Friendly Cyanide Source

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